Key Clinical Takeaways from a Prospective RCT
Philip R Judge BVSc MVS PG Cert Vet Stud MACVS (VECC, Medicine of Dogs)
The following are key findings based on the prospective, randomised, double-blinded, placebo-controlled study by Splittstoesser et al. (2021–2025) of 80 male cats with first-time urethral obstruction.
About the Study
Treatment duration
Cats were treated with lorazepam (or placebo) for 30 days after hospital discharge. The study medication was dispensed for a 30-day course, and follow-up assessments were conducted on days 7, 15, and 30 after starting the medication. The study evaluated recurrence and lower urinary tract signs during this 30-day period.
Dose
The dose administered was half of a 0.5 mg tablet (0.25 mg) per cat, given orally every 12 hours. This equates to approximately 0.05 mg/kg per dose, though the authors note this is an approximation based on an average cat weight.
Administration details
- The first dose could be given while the cat was still hospitalised (if amenable to oral medication) or upon discharge with the owner.
- The study drug was compounded into identical-appearing placebo tablets of the same size, shape, and colour to maintain blinding.
- Owners were contacted on days 7, 15, and 30 using standardised questions to assess adverse effects, LUT signs, and recurrence.
Note
The study specifically excluded cats with urolithiasis, urinary tract infection, previous urethral obstruction, or concurrent steroid/NSAID use. The results apply to first-time obstructed male cats without these comorbidities, receiving a multimodal protocol including prescription diet and environmental modification. The authors recommend larger studies to further validate this treatment approach.
1. Lorazepam significantly reduced the 30-day recurrence rate of urethral obstruction to zero
In this study, no cats receiving lorazepam experienced recurrence of urethral obstruction within 30 days (0%; 95% CI, 0.0% to 10.9%), compared with 15.7% (5 of 35 cats; 95% CI, 5.2% to 33.7%) in the placebo group. This difference was statistically significant (P = 0.016).
The recurrence rate in the placebo group was lower than many previously reported rates (18%–66%), which the authors attribute to the multimodal management approach used in the study, including prescription diet and environmental modification.
2. The proposed mechanism targets skeletal muscle of the distal urethra
The most common sites of urethral obstruction are the prostatic and post-prostatic (distal) urethra, which are primarily composed of skeletal muscle. Lorazepam, a benzodiazepine, potentiates the inhibitory effects of GABA, providing skeletal muscle relaxant effects. Previous alpha-blockers such as prazosin and phenoxybenzamine target smooth muscle of the proximal urethra, which the authors suggest may be less physiologically relevant for preventing distal urethral obstruction. Skeletal muscle relaxation, combined with anxiolytic effects, forms the therapeutic rationale for lorazepam use.
3. Lorazepam reduced owner-reported lower urinary tract signs in the second and third weeks after discharge
Lower urinary tract signs were significantly reduced in the lorazepam group during days 8 to 15 (6% vs 29%; P = 0.034) and days 16 to 30 (3% vs 22%; P = 0.042). The overall proportion of cats with LUT signs was lower in the lorazepam group (27.8%) than the placebo group (51.4%), but this difference did not reach statistical significance (P = 0.054). Most LUT signs in the lorazepam group occurred within the first 7 days (28%), suggesting that the skeletal muscle relaxant effects may contribute to decreased urethral spasms beyond the immediate post-obstruction period.
4. Lorazepam was well tolerated; ataxia was the only statistically significant side effect
Ataxia was reported in 13% (4 of 31 cats) of the lorazepam group and 0% of the placebo group (P = 0.046). Sedation was reported in 26% of the lorazepam group and 9% of the placebo group, but this difference was not statistically significant (P = 0.099). Increased appetite (16% vs 3%; P = 0.095) and vocalisation (13% vs 3%; P = 0.18) were also not significantly different between groups. The authors note that lorazepam is primarily excreted as a glucuronide conjugate in cats, suggesting it may avoid the idiosyncratic acute hepatic necrosis reported with oral diazepam, although liver enzymes were not monitored in this study.
5. Study design and limitations affect generalisability
The study used a standardised multimodal protocol that may not reflect routine practice: all cats received prescription urinary diet (Hill’s c/d Multicare), owner education on environmental modification, and analgesia (buprenorphine, and gabapentin or acepromazine as needed).
Exclusion criteria included urolithiasis, urinary tract infection, and prior obstruction.
Limitations of the study include non-standardised initial treatment at clinician discretion, absence of cystourethrography to rule out strictures or uroliths, small sample size (72 completed), and lack of a validated scale for owner-reported side effects.
The study was closed early due to low accrual, and the authors recommend larger multicentre studies to validate these findings.
Additional clinical points from the study:
- Of the 5 cats with recurrence in the placebo group, 3 underwent perineal urethrostomy.
- Lorazepam’s safety profile in this study was favourable, though the study was not powered to detect rare adverse effects.
- The authors suggest lorazepam may offer dual benefits: skeletal muscle relaxation of the distal urethra and anxiolysis, both relevant to feline idiopathic cystitis and urethral obstruction.
- The study was supported by Hill’s Science Diet, who donated the prescription diet used.
Reference:
Splittstoesser A, Kerley J, Lulich J, Randall A, Tart K. Lorazepam reduces recurrence of urethral obstruction in male cats: a prospective, randomized, double-blinded, placebo-controlled study. Journal of the American Veterinary Medical Association. 2026 May 6;1(aop):1-9.
